POS1217 CCL-18 AS A BIOMARKER OF INTERSTITIAL LUNG DISEASE (ILD) AND PROGRESSIVE FIBROSING ILD IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES
Authors: E. Zanatta, R. Depascale, A. Gamba, M. Tonello, A. Martini, M. Gatto, A. Doria, L. Iaccarino
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interstitial lung disease (ILD) is the most frequent organ involvement in patients with idiopathic inflammatory myopathies (IIMs). Some patients with connective tissue diseases including IIMs may develop a progressive fibrosing (PF-)ILD [1]. The chemokine CCL18 is constitutively expressed by dendritic cells and macrophages in lung tissues and may induce collagen synthesis in lung fibroblasts. Circulating CCL18 correlated with fibrosis severity in idiopathic pulmonary fibrosis and it predicts ILD progression in patients with systemic sclerosis (SSc) [2]. OX40 ligand (OX40L) is a glycoprotein expressed on activated antigen-presenting cells and in vivo OX40L blockade prevents inflammation-driven skin, lung, and vessels fibrosis in mouse models of SSc [3]. <h3>Objectives</h3> To assess the potential role of CCL-18 and OX40L as biomarkers of ILD and PF-ILD in patients with IIMs. <h3>Methods</h3> Patients affected with IIMs (EULAR/ACR 2017 criteria) followed in our referral center were consecutively enrolled from September 2020 to March 2021. Clinical and serological variables, and organ involvement were recorded. Pulmonary involvement was investigated by high-resolution CT (HRCT) and pulmonary function tests (PFTs). CCL-18 (pg/ml) and OX40L (pg/ml) serum levels were measured by validated ELISA assays (according to the manufacturer's instructions) in patients and in 35 controls (matched for age and sex). Follow-up data including worsening of respiratory symptoms, and repeated PFTs and HRCT were recorded. PF-ILD was defined according to the INBUILD criteria [1]. <h3>Results</h3> Ninety-three IIMs patients (64.5% females) with median age 62 (IQR 54.5-71) years and disease duration 3 (IQR 2-9) years were enrolled; ILD was detected in 52 (54.7%) patients. OX40L serum levels were similar between patients and controls, whereas CCL-18 serum levels were higher in IIMs patients than in controls (232.9 [IQR 134.7-399.07] vs. 48.4 [IQR 29.9-147.5], p&lt;0.0001, <b>Figure 1A</b>). Among IIMs patients, those with ILD exhibited higher levels of CCL-18 than those without (305.6 [181.6-518] vs. 164.3 [79.6-270.7], p=0.001, <b>Figure 1B</b>). No association between CCL-18 values with autoantibodies, PFTs or any other clinical features was detected. During follow-up 16/52 (31%) patients developed a PF-ILD. At baseline, patients who developed PF-ILD had higher CCL-18 serum levels than non-progressors (306.4 [198.9-621.9] vs. 207.8 [102.6-376.8], p=0.03]. Higher CCL-18 values, Anti-Ro52 and anti-MDA5 positivity, lower Creatine Kinase levels and diffusing capacity for carbon monoxide (DLCO) values were predictors of PF-ILD occurrence at univariate but not at multivariate analysis. <h3>Conclusion</h3> CCL-18 but not OX40L may be a useful biomarker in the assessment of patients with IIMs-ILD. <h3>References</h3> [1]Flaherty KR et al, N Engl J Med 2019;381(18):1718-1727. [2]Schupp J et al, Eur Respir J 2014;43(5):1530-2. [3]Elhai M et al, Proc Natl Acad Sci USA 2016;113:E3901-10. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.